CHAMGAP
APPROVEDReviewed and approved by the Chamgap Editorial Team (2026-07-23). The draft was written by AI, the existence of all 2 cited sources was verified at the original page, and the verdict passed blind grading and adversarial audit. Methodology v0.6.
Verdict No. 1326 · Search date 2026-07-23 · Methodology v0.6

Seladelpar,
does it really help with Improved ALP-bilirubin biochemical response and pruritus in primary biliary cholangitis with inadequate UDCA response?

30-Second Summary
C
Evidence Grade C · 54 · Safety unknown
Seladelpar improves laboratory response and pruritus in PBC, but effects on transplantation, liver failure, and survival remain unconfirmed
What the
research shows
Seladelpar is rated C because it improves biochemical response and pruritus in primary biliary cholangitis with inadequate response or intolerance to UDCA. In the 12-month RESPONSE trial, the composite ALP-bilirubin biochemical response was 61.7% versus 20.0%, and the six-month pruritus NRS change among participants with moderate-to-severe itch favored seladelpar at -3.2 versus -1.7. The pivotal efficacy outcomes were nevertheless biochemical surrogates and a subjective symptom; the trial was not designed or powered to establish fewer transplants, liver failure events, or deaths. Rule ① therefore yields C with 54 points.
What the
ads claim
Promotion can translate lower ALP and bilirubin directly into stopped disease progression or longer survival. The directly established range is biochemical response and relief of pruritus.
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Useful facts when choosing a product

  • Seladelpar is a prescription drug used with UDCA in adults with inadequate UDCA response, or alone when UDCA is not tolerated.
  • The United States label recommends 10 mg once daily with or without food and does not recommend use in decompensated cirrhosis.
  • Liver tests are obtained before and during treatment, and treatment is interrupted while suspected biliary obstruction is evaluated.
  • Common adverse reactions include headache, abdominal pain, nausea, abdominal distension, and dizziness; abnormal liver tests and symptoms of myalgia or myopathy also require monitoring.
Gap Measurement · Verdict 1326 · C 54
What advertising claims
What independent, higher-quality research supports
△ GAP
01

What the research actually shows

The RESPONSE Study Group randomized 193 patients with PBC and inadequate response or intolerance to UDCA in a 2:1 ratio to seladelpar 10 mg or placebo. The 12-month composite biochemical response was 61.7% versus 20.0%, and ALP normalization was 25.0% versus 0%. Among 49 and 23 participants with baseline NRS scores of at least 4, the six-month pruritus changes were -3.2 and -1.7. ENHANCE was stopped early because of an erroneous safety signal in a different liver-disease trial, but its blinded three-month analysis found biochemical response rates of 78.2% versus 12.5% and pruritus changes of -3.14 versus -1.55 for 10 mg and placebo. Neither trial had the event count or follow-up to establish transplantation, liver failure, or survival effects.

02

Why this is classified as C (54)

The 61.7% versus 20.0% biochemical response and pruritus NRS difference in RESPONSE provide direct positive randomized evidence. ALP and bilirubin remain surrogates, pruritus is subjective, and effects on transplantation, liver failure, and survival are unconfirmed, producing C with 54 points under rule ①.

Counterpoint. Symptom and laboratory improvement has clinical value but does not establish fewer long-term clinical events. Specialist assessment of disease stage and liver tests remains necessary.

Rejudgment record. Cross-check applied — Accepted the RESPONSE biochemical response of 61.7% versus 20.0% and pruritus improvement, but applied the rule ① ceiling of C because only ALP-bilirubin surrogates and a subjective symptom are established while transplantation, liver failure, and survival remain unconfirmed

Sub-claim grades by effect

This ingredient is marketed for several effects. A single overall grade blends strong and weak claims together, so each effect is graded separately here. The overall grade reflects the strongest disconfirming or core claim.

Effect (sub-claim)GradeBasis
Improved composite ALP-bilirubin biochemical responseCRESPONSE found 61.7% versus 20.0%, but this is a surrogate rather than a long-term clinical event.
Improved pruritus in PBCCThe NRS declined more than placebo among participants with moderate-to-severe itch, but it is subjective and subgroup based.
Improved transplantation, liver-failure, or survival outcomesCCurrent trials were not designed or powered to establish these hard clinical outcomes.

Cross-check — Codex and Claude

This verdict was drafted by Codex through literature review and source-existence checks, cross-checked through blind grading and adversarial audit, and settled by reapplying the methodology boundary rules. Cases with split grades were resolved through rejudgment.
03

Evidence Table

StudyDesignSampleFundingEndpointResultWeight
Hirschfield GM et al.; RESPONSE Study Group. 2024 RESPONSEMulticenter randomized double-blind placebo-controlled phase 3 trial193Sponsored by CymaBay TherapeuticsTwelve-month composite ALP-bilirubin biochemical response; six-month pruritus NRSBiochemical response was 61.7% versus 20.0%; the pruritus NRS change was -3.2 versus -1.7 in the moderate-to-severe itch subgroup.Pivotal phase 3 surrogate and symptom evidence
Hirschfield GM et al.; ENHANCE Study Group. 2023 ENHANCEBlinded three-month analysis of an early-terminated randomized double-blind placebo-controlled phase 3 trial87Sponsored by CymaBay TherapeuticsComposite biochemical response, ALP normalization, and pruritus NRSAt three months, the 10-mg biochemical response was 78.2% versus 12.5%, with pruritus changes of -3.14 versus -1.55.Concordant but early-terminated and short-term
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Receipt — 2 References

All 2 cited sources were verified for existence at the original page (as of 2026-07-23).

Hirschfield GM, Bowlus CL, Mayo MJ, et al.; RESPONSE Study Group. A Phase 3 Trial of Seladelpar in Primary Biliary Cholangitis. N Engl J Med. 2024;390(9):783-794. PMID: 38381664. DOI: 10.1056/NEJMoa2312100.
checked
Hirschfield GM, Shiffman ML, Gulamhusein A, et al.; ENHANCE Study Group. Seladelpar efficacy and safety at 3 months in patients with primary biliary cholangitis: ENHANCE, a phase 3, randomized, placebo-controlled study. Hepatology. 2023;78(2):397-415. PMID: 37386786. PMCID: PMC10344437. DOI: 10.1097/HEP.0000000000000395.
checked
Draft and rewrite: Codex (AI) · Verification: Codex blind grading and adversarial audit · Final adjudication: Claude
Reviewed and approved: Chamgap Editorial Team · Approval date: 2026-07-23 · Corrections: none

Cite this verdict

Seladelpar x improved biochemical response and pruritus in PBC with inadequate UDCA response Evidence Grade C card
[Chamgap] Seladelpar x improved biochemical response and pruritus in PBC with inadequate UDCA response — Evidence Grade C·54. 2 cited sources checked. Source: https://chamgap.com/en/verdicts/liver/seladelpar-udca-inadequate-pbc-biochemical-response-pruritus/ · CC BY 4.0

CC BY 4.0 — free to use with attribution; do not distort grades, numbers, or verdict meaning.

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What this document does and does not do

Chamgap is an information source. It reports what research has and has not confirmed; it does not tell readers what to take or buy. That decision belongs to readers and, when needed, medical or legal professionals. This verdict reflects literature available up to the search date and may change as new research appears. Nothing here is medical advice.